Antimycotic compositions comprising chloromethyl 5-nitro-2-furyl ketone



United States Patent 6 s5 ANTIMYCOTIC COMPOSITIONS COMPRISING CHLOROIVETHY L S-NITRO-Z-FURYL KET ONE Joseph Edward Gray and Russell Youker Mosher, Norwich, N.Y., assignors to The Norwich Pharmacal Company, a corporation of New York N0 Drawing. Filed Aug. 22, 1962, Set. No. 218,517

' 5 Claims. (Cl. 167-64) ketone useful for combatting mycotic vulvovaginitis Still more particularly, this invention is concerned with a vaginal suppository efiective in the control of mycotic vulvovaginitis.

Mycotic vulvovaginitis is characterized by pruritus which is oftentimes mild but may become persistent and unrelenting causing great discomfiture and embarrassment. Etiologically this condition may arise from the use of broad spectrum antibiotics which sometimes change the vaginal flora permitting the emergence and overgrowth of fungi. Pregnancy is oftentimes a predisposing factor to vulvovaginal infection by certain fungi. Among the fungi most often causative of this condition, Candida albicans is predominant.

Other species, such as Candida guilliermondi, Candida tropicalis, Candida krusei, Candida parakrusei and Torulopsis glabrata, are frequently involved. Eradication of these microorganisms is necessary to secure relief. This is most conveniently and effectively accomplished by topical medication.

Numerous topical medicaments have been employed in the treatment of vulvovaginitis. That their use has not been wholly successful is underlined by the continued search for agents which are specifically and highly effective against the causative microorganisms and which maintain this degree of effectiveness in repetitive usage.

We have discovered that chloromethyl 'S-nitro-Z-furyl ketone is surprisingly highly active against those organisms involved in mycotic vulvovaginitis and that its great efiiciency in this respect may be made available through in corporation in acceptable pharmaceutical vehicles to provide topical compositions which are readily and conveniently applicable to the'infeoted site.

In accordance with our invention, we prefer the suppository as the most convenient form for administering chloromethyl-S-nitro-Z-furyl ketone. As a suppository base those materials known to the apothecary art for such purpose may be used. We prefenhowever, to use a base which is hydrophilic and readily adrnixable with vaginal secretions thereby permitting optimal release of the active agent.

Suitable hydrophilic. base materials consist of the solid polyethylene glycols, the solid polypropylene glycols, and the polyoxyethylene esters of palmitic, stearic and myristic acid. An exemplary composition of our invention is:

Parts by Ingredient: weight '(A) Polyoxyethylene palmitate containing 20 oxyethylene units per mol 13.80

(B) Polyethylene glycol of average molecular weight 1000 86.15 (C) Chloromethyl 5nitro-2-furyl ketone 0.05

In the use of our compositions comprising chloromethyl-S-nitro-Z-furyl ketone, for instance, in suppository form as exemplified above, for the control of vulvovaginitis, we have found it advantageous to add a small amount of an acid, such as hydrochloric, to pose a slightly acid medium. It is generally believed that vaginal infections are, in part, traceable to and complicated by a shift in normal vaginal pH toward the alkaline side. Maintenance of pH on the acid side is, therefore, beneficial when vaginal infection is being treated to present,

insofar as possible, a physiologic pH locale so that unwanted and infectious producing agents resident therein may be dealt with in most expeditious fashion.

The amount of hydrochloric acid which we deem to be an advantageous additament to our antimycotic compositions is very small. In the hereinabove exemplified suppository form the (addition of as little as 0.028 part by weight of concentrated hydrochloric acid is sufficient to accomplish the desired purpose. Such addition is conveniently accomplished in accordance with the preparation of the exampled composition by introducing the acid into the melt prior to pouring into the suppository mold. Concornitantly, we have noted that .the addition of small amounts of such an acid, while producing an acid vaginal suppository considered to be desirable in the treatment of vaginitis for reasons hereinbefore alluded to, also evokes a salutary effect upon the appearance and general shelf-life of our suppository composition.

What is claimed is:

1. An antimycotic vaginal suppository comprising a baseof polyoxyethylene wax and about 0.05% by weight thereof of chloromethyl 5-nitro-2furyl ketone.

2. An acid antimycotic vaginal suppository comprising (1) a base of polyoxyethylene wax; (2) about 0.05% by weight thereof of chloromethyl 5-nitro-2-furyl ketone; and

.(3) about 0.028% by weight thereof of concentrated hydrochloric acid.

3. An acid antimycotic vaginal suppository comprising 13.80 parts by weight of polyoxyethylene palmitate containing 20 oxyethylene units per mol; 86.122 parts by weight of a polyethylene glycol Wax having an average molecular weight of 1000; 0.05 part by weight of chloromethyl S-nitro-Z-furyl ketone and 0.028 part by Weight of concentrated hydrochloric acid.

4. The method of combatting mycotic vulvovaginitis which comprises the intravaginal administration to an infected host of an antimycotic suppository containing as active agent chloromethyl 5-nitro-2- furyl ketone.

5. The method of combatting mycotic vulvovaginitis which comprises the intravaginal administration to an infected host of an acid antimycotic suppository containing chloromethyl 5-nitro-2-furyl ketone as the active antifungal agent and concentrated hydrochloric acid as the acid posing agent.

References Citedin the file of this patent UNITED STATES PATENTS Stillman et al May 18, 1943 Hayes et al Mar. 21, 1961 OTHER REFERENCES 

1. AN ANTIMYCOTIC VAGINAL SUPPOSITORY COMPRISING A BASE OF POLYOXYETHYLENE WAX AND ABOUT 0.05% BY WEIGHT THEREOF OF CHLOROMETHYL 5-NITRO-2-FURYL KETONE. 